Glycosyltransferases (GTs) constitute a superfamily of ubiquitous enzymes that attach carbohydrate moieties to biological molecules(1), and thus, play a role in the biosynthesis of oligosaccharides(2), glycosaminoglycans(3), glycopeptides(4), and glycosylated anticancer/anti-infective agents(5). These enzymes are generally perceived as unidirectional catalysts that drive the formation of glycosidic bonds from nucleotide sugar (NDP-sugar) donors and aglycon acceptors(6).
In practice, these sugar-containing moieties include anticancer agents (the enediyne calicheamicin, CLM), anthelmintic agents (the macrolide avermectin, ivermectin and erythromycin) and antibiotic agents (the glycopeptide vancomycin, VCM) among other compounds. Typically these natural product-based drugs are synthesized by unidirectional GT-catalyzed reactions. However, based on the broad spectrum application of these compounds, a greater diversity and availability of combinatorial library of these compounds is desirable.
GTs are likely involved in the biosynthesis of anticancer (the enediyne calicheamicin, CLM), anthelmintic (the macrolide avermectin, AVR, ivermectin, and erythromycin) and antibiotic (the glycopeptide vancomycin, VCM) natural product-based drugs which catalyze reversible, bidirectional reactions.
Therefore, a need exists for mechanisms for introducing novel sugar moieties and conjugating these moieties with varied aglycons to generate biocombinatorial libraries of these compounds.